Many Who Start Antipsychotics Discontinue Treatment

More than a third of people with Parkinson’s disease who are prescribed antipsychotics stop treatment within six months of starting, a new database analysis suggests.

The data also indicate that rates of treatment discontinuation are lower with Nuplazid (pimavanserin) than with other antipsychotics.

The findings were published in BMC Neurology in the study “Low continuation of antipsychotic therapy in Parkinson disease – intolerance, ineffectiveness, or inertia?”

Up to 60% of those with Parkinson’s will experience psychosis — sensing things that are not real (hallucinations) and/or irrational beliefs not based in reality (delusions). Antipsychotics are a class of medications used to treat psychosis. The use of these medications in Parkinson’s patients is complicated, however, because antipsychotics modulate the activity of dopamine, which is abnormally low in Parkinson’s. As a result, some antipsychotics can cause symptoms of Parkinson’s to worsen.

Nuplazid was approved in the U.S. in 2016 as a treatment specifically for Parkinson’s-related psychosis. Other antipsychotics — including clozapine, quetiapine, risperidone, olanzapine, and aripiprazole — are sometimes used off-label (in the absence of regulatory approval) to manage Parkinson’s psychosis.

In the new study, a team of scientists at the University of Pennsylvania analyzed an insurance database. Based on insurance claims for specific medications, they identified 3,566 people with Parkinson’s who started treatment with an antipsychotic from 2001 to 2019. Of those, 153 were new users of Nuplazid, 2,452 of quetiapine, 169 of aripiprazole, 462 of risperidone, and 304 of olanzapine. Clozapine use was extremely rare (26 patients) and was excluded from the analyses.

The researchers looked at discontinuation rates — the percentage of patients who no longer were being treated with any antipsychotics, six months after they started treatment. Results showed a discontinuation rate of more than one-third (38.6%).

Overall discontinuation rates were lowest (22%) among participants who started on treatment with Nuplazid, relative to those who started on other antipsychotics. Median time to discontinuation also was generally longer for Nuplazid (168 days) than other antipsychotics (mostly less than 100 days).

Further statistical analyses demonstrated that, compared to Nuplazid, the likelihood of treatment discontinuation was about twice as high with all other antipsychotics analyzed.

Overall discontinuation rates also were significantly lower among younger patients and among females.

A smaller proportion of patients (6%) switched from one antipsychotic therapy to another, rather than discontinuing treatment altogether. The lowest rate of switching was seen among patients who started treatment with quetiapine (4.9%), and most patients who switched therapies moved from another antipsychotic to quetiapine.

Statistical analyses showed that the likelihood of switching was significantly lower among patients 80 or older, and that the likelihood of switching was significantly lower with Nuplazid than with other medications.

The researchers noted several possible explanations for their findings. For example, they noted that some patients may be discontinuing antipsychotic treatment because they were experiencing an acute psychotic episode that was treated successfully, so they don’t need further treatment. However, further examination of the data suggested this was unlikely, since most patients didn’t have anything in their records indicating an acute episode prior to being prescribed the antipsychotic.

Other possible explanations include ineffectiveness — the therapy wasn’t working, or wasn’t working as well as hoped — and intolerance, meaning side-effects or other safety issues precluded continuing treatment.

More studies are needed to “parse the contributing effects of treatment intolerance or ineffectiveness, prescribing appropriateness, patient non-adherence, and symptom resolution on psychosis treatment patterns,” the researchers concluded.

A noted limitation of this study is its use of insurance data, which means the researchers didn’t have access to some clinical information (e.g., the severity of psychosis symptoms before and after treatment). Also, by definition, the data are reflective only of people with private insurance, which may not represent the whole patient population.

Nuplazid is marketed by Acadia Pharmaceuticals, which was not involved with this study. However, two authors disclosed they have received financial support from Acadia.